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Jeffrey H. Silverstein, M.D.
West Nyack, New York
Alterations in the brain following anesthesia and surgery have become the new vogue. Indications that some patients were experiencing significant alterations where first reported in the 1950’s. Partly because anesthesia has become significantly safer, because we are operating on an increasingly elder population, and because of advances in cognitive neurosciences, there has been a wealth of recent interest in two major central nervous system disorders, postoperative delirium and postoperative cognitive dysfunction (POCD). A recent review covers the current understanding of both of these entities.
1
Grossly, brains shrink with age, the amount of total atrophy varying greatly. Neurogenesis has been identified in multiple mammalian species in multiple areas of the brain.
2 The role, if any, that neurogensis plays in the aging brain or in recovery from brain injury is unclear. The role of neurogenesis in CNS functions, such as memory formation, is under intense scrutiny. Several studies have suggested that newly developed neurons are associated with learning and memory in rat hippocampus.
Imaging technology has greatly expanded our ability to evaluate the aging brain, suggesting, as an example that while gray matter decreases progressively with age, white matter increases, peaking in the 50’s before decline is noted.
3 FDG PET imaging has been used to show that while whole brain metabolism decreases with age, this is primarily due to alterations in the frontal lobes, while the metabolism of the cerebellum is more or less maintained.
4
The concept of cognitive reserve has been put forward to explain the common finding of significant change on images of individual brains before any behavioral effects are noted. Years or level of education is believed to be a surrogate measure of cognitive reserve. Level of education has been a persistent factor related to the development of delirium and postoperative cognitive dysfunction.
On a functional basis, hearing loss is common, with marked loss for sounds > 8000Hz. Sight decreases with a decrease in light sensitivity, relative loss of blue and green color perception, decreased reading speed and altered visual search strategies. Simple reaction times are frequently maintained but complex reaction time, in which a distinction or decision must be made is frequently slower. Fluid intelligence, associated with adaptability or flexibility is decreased but crystallized intelligence (experience, wisdom) may be increased. Research on the impact of senescence on pain is desperately needed. Recently, Farrell and Gibson reported that that aging impacts on the capacity of the nociceptive system to down-regulate subsequent to sensitization.
5 This finding is consistent with the prolonged and chronic symptoms frequently reported by the elderly. Pain and pain treatment are thought the be intimately involved in the development of delirium, so further understanding of these differences may be important to understanding neurocognitive disorders.
Delirium is defined by the Oxford English Dictionary as “A disordered state of the mental faculties resulting from disturbance of the functions of the brain, and characterized by incoherent speech, hallucinations, restlessness, and frenzied or maniacal excitement.”. The 4 th edition of the Diagnostic and Statistical Manual for Mental Disorders
(DSM IV) indicates that the key features of delirium are: 1) that it is a change in mental status, characterized by a prominent disturbance of attention and reduced clarity of awareness of the environment; and 2) that it has an acute onset, developing within hours to days, and tends to fluctuate during the course of the day. Both of these definitions refer to some functional change in the brain that is not specified. What is specified is the behavior; precise characterization of this behavior has been crucial for delirium research. An important limitation of defining delirium is the difficulty associated with the assessment of ordered thought and consciousness.
Delirious behavior is seen in the perioperative period at two primary times. During emergence from general anesthesia, a small percentage of patients exhibit dis-inhibited behavior and are unresponsive to verbal commands.
This is frequently accompanied by physical movement that can be difficult to control and appears to be of a strength out of proportion to that expected from the patient. This phenomenon is commonly referred to as emergence delirium, although some authors have suggested that agitation or excitation is more appropriate, given the inability

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6 The reported incidences are extremely varied, ranging from 10% to 80%. The etiology remains unknown although many ideas have been contemplated. Importantly, emergence delirium is generally self-limited without the need for additional medication. A variety of rescue mediations have been used including essentially all analgesics, hypnotics, and benzodiazepines and early reunion with the parent all appear effective for children. Potentially effective attempts to prevent emergence delirium include use of prophylactic benzodiazepines or dexmedetomidine.
Much more research on this area is needed to provide evidence-based guidance on the management of emergence delirium.
Elderly patients are prone to a distinct form of delirium that is not immediately linked to emergence from anesthesia.
Although the severity of agitation varies, it often presents in a hypoactive, rather than a hyperactive form and is commonly seen between 24 and 72 hours following their operation, often following a significant period of lucidity.
This form of delirium has been most commonly referred to as postoperative delirium but it has also been call interval delirium and has, in some literature, been confused with postoperative cognitive dysfunction, which is a distinct, if potentially related entity. Similar neuropsychiatric dysfunction is noted in the intensive care unit. For many years this was described as ICU psychosis and was a diagnosis of exclusion. Currently this area has been greatly defined by Dr. Wes Ely and colleagues as ICU delirium.
7
A significant advancement in the area of delirium was the development of standard instrument for defining the delirious state. Although controversy still exists, particularly in regard to the evaluation of severity, the Confusion
Assessment Method (CAM) developed by Sharon Inouye has become the standard for the present/absent definition of delirium.
8 Dr. Ely modified Dr. Inouye’s instrument to formulate the CAM-ICU.
9 Using the CAM, the incidence of delirium following general anesthesia is approximately 5-15%.
10 Patients with hip fractures appear to have a higher incidence, with an average of approximately 35%.
11 It is important to understand that there is a similar incidence of delirium in elderly patients hospitalized for medical illness, so the role of anesthesia per se is not clear.
At the current time, the primary risk factors for delirium described in surgical patients are: age > 70, prior history of delirium, history of alcohol abuse, preoperative use of narcotic analgesics, and preoperative depression, greater intraoperative blood loss, more postoperative transfusions, postoperative hematocrit < 30%, and severe postoperative pain.
12,13;14
The direct effect of perioperative drugs has been difficult to ascertain. Although a number of theories have been advanced, the etiology of delirium is not understood, as no clear treatment has evolved.
Preventive measures based on intensive geriatric care have been shown to decrease the incidence by about 1/3.
15;16
Choice of anesthetic technique, particularly the choice of regional versus general anesthesia, has not be found to influence the incidence of delirium
The treatment of agitation and disruptive behavior generated by a patient’s hallucinatory conception of their surroundings is particularly challenging. If at all possible, physical restraints should be avoided. It is important to prevent injury to the patient and to protect staff. When i.v. access is available, intravenous haloperidol (0.5-1mg) is still the primary drug of choice for achieving manageable sedation of these patients. It is important to avoid over sedating the patient, as haloperidol is a prolonged half-life (up to 72 hours) in the elderly. Benzodiazepines can sometimes be effective, particularly if alcohol withdrawal is involved, however paradoxical reactions may also occur, thus making the situation worse. In speaking with delirious patients, it is suggested that the physician present a very clear sense of current reality without specifically stating that their something wrong with the patient. Telling the patient that they are delirious is rarely useful.
Fortunately, delirium is usually self-limiting. The relationship between delirium and POCD is not clear. There are anecdotal reports of patients developing postoperative delirium and subsequently manifesting severe cognitive change. To date, this phenomenon has not been particularly well characterized in clinical studies. The cost of providing care to delirious patient is significant with an average additional 1.4 days in the hospital stay and $2947 in patient care costs per incident.
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Postoperative Cognitive Dysfunction (POCD) has come to represent any type of neurocognitive change that can be detected following anesthesia and surgery. The types of effects reported wary widely. An impressive literary account is found in Larry McMurtry’s memoir in which he described the three year experience of not being able to read for three years following his heart surgery.
18 Many anecdotal reports describe changes that might be characterized as changes in personality. However, these types of changes have never been coherently studied or characterized. What has been reasonably well characterized, and what researchers in the field refer to as POCD, are changes in neuropsychological tests that can be documented by testing patients before and at varying times after surgery. The tests used can be grouped into the general categories of memory and executive dysfunction. The amount of change that is called dysfunction is not standardized, however a careful analysis of the data permits some degree of comparison. Investigators that measure function in the immediate postoperative period, i.e the first few days following surgery, tend to find a significant incidence of dysfunction.
19 As the test moves further from the date of surgery, the incidence of POCD declines and probably becomes indistinguishable from the general population after a few years. Studies of POCD have tended to separate patients undergoing open heart surgery versus all other types of surgery. An overview of the current literature for non-cardiac surgery suggests that about 25% of patients will be significantly different immediately following surgery, the incidence decline to about 10% of patients, 5% at
6 months and perhaps 1% at 1 year.
20,1
For cardiac surgery, the incidence appears to be higher and slightly more durable, although recent literature suggests that there is no difference between cardiac surgery and pecutaneous cardiac interventions. For years, the role of the cardiopulmonary bypass was thought to be of primary importance in the development POCD following cardiac surgery, however recent reports suggest that off-pump procedures have a similar incidence.
21
It is important to understand that any disability associated with the types of changes measured with current testing batteries is highly individualistic. Individuals with jobs that require extensive cognitive work will notice impairment more than individuals who are retired with limited activities. Recent data from Monk et. al. confirmed that persistent POCD is primarily a problem of elderly patients suggest that patients with POCD have an increased mortality.
22 Price reported that more older adults experienced memory decline at 3 months, but only those with executive or combined cognitive decline had functional limitations.
23 Previous studies have suggested that changes in cognitive function have also been associated with decreased capacities in ADLs and IADLs. (activities and independent activities of daily living).
The etiology of POCD remains unclear. We do not know whether surgical illness is different than medical illness as similar studies are hard to accomplish in medical ill patients (because it is hard to test them before they get sick). To date, nothing has been found that will either decrease the incidence or successfully treat POCD. The clinical significance has only been implied, and it difficult to counsel patients currently as to the risk of POCD or any potential treatments. Most significantly, in spite of multiple randomized well conducted studies, there appears to be no clear difference between regional and general anesthesia.
24
In order to properly understand the role of POCD in clinical anesthesia care, significant additional information will need to be developed.

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